title: Novel FIG4 mutations in Yunis-Varon syndrome.
abstract: Yunis-Varon syndrome (YVS, MIM 216340) is a rare autosomal recessive disorder characterized by skeletal abnormalities and severe neurological impairment with vacuolation of the central nervous system, skeletal muscles and cartilages. Very recently, mutations of the FIG4 (FIG4 homolog, SAC1 lipid phosphatase domain containing (Saccharomyces cerevisiae)) gene, which encodes a 5'-phosphoinositide phosphatase essential for endosome/lysosome function have been identified as the cause for YVS. Interestingly, FIG4 mutations were previously reported to be responsible for other neurodegenerative diseases such as autosomal recessive Charcot-Marie-Tooth disease type 4J and autosomal dominant amyotrophic lateral sclerosis/primary lateral sclerosis. We analyzed a YVS patient using whole-exome sequencing, and identified novel biallelic FIG4 mutations: c.1750+1delG and c.2284_2285delCT (p.S762Wfs*3). These two mutations were mutations supposed to have null function. To our knowledge, this is the second report of FIG4 mutations in YVS and our result supports the idea that biallelic null mutations of FIG4 cause YVS in human.
authors.affiliation: 1] Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan [2] Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Nakajima
authors.affiliation: Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shiraishi
authors.affiliation: Department of Radiology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Pediatrics, Tokyo Medical University, Shinjuku, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
mesh_terms: D002675:Child, Preschool; D002973:Cleidocranial Dysplasia / Q000235:genetics*; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D005420:Flavoproteins / Q000235:genetics*; D006801:Humans; D017880:Limb Deformities, Congenital / Q000235:genetics*; D008844:Micrognathism / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases
chemical_list: D005420:Flavoproteins; C522215:FIG4 protein, human; D010744:Phosphoric Monoester Hydrolases